Cefazolin sodium, its full name is: Monosodium (6R,7R)-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)thio]methyl]-7-(1H-tetrazol-1-yl)acetyla mino]-8-oxo-5-thia-1-azabicyclo[4.2.0]-oct-2-ene-2-carboxylate, its chemical formula is C14H14N8O4S3, its pentahydrated compound has a structure formula as shown in FIG. 1, being white or near white crystalline powder, with a molecular weight of 566.57, and a theoretical water content of 15.9%; it is freely soluble in water, slightly soluble in methanol and ethanol, and practically insoluble in isopropanol, acetone, chloroform, dichloromethane and ethyl acetate; it has no fixed melting point, and its decomposition temperature is 193±2° C.
Cefazolin sodium is the first generation of broad-spectrum antibiotic, it exhibits excellent antibacterial activity to Gram-positive coccus, except enterococcus, methicillin-resistant staphylococcus. Streptococcus pneumoniae and streptococcus haemolytica are highly sensitive to this product. Corynebacterium diphtheriae, bacillus anthracis, listeria and clostridium are also very sensitive to this product. This product has good antibacterial activity to partial E.coli, proteus mirabilis and klebsiella pneumoniae, but has low antibacterial activity to actistaphylococcus. Typhoid bacillus, shigella and neisseria are sensitive to this product, but other enterobacteriaceae, acinetobacter and P. aeruginosa are resistant to this product. PPNG (Penicillinase-Producing Neisseria gonorrheae) is resistant to this product. Haemophilus influenzae only exhibits intermediate sensitivity. With the enhancement of the standard of living of common people and domestic production level, recently, the demand of cefazolin sodium has been increased continuously.
At present, it has been known that cefazolin sodium has 4 crystalline forms, i.e., α-crystal, β-crystal, γ-crystal, and amorphous crystal forms, in which α-crystal of cefazolin sodium is present in needle crystal, with a specific rotation of −20°-−25°, and absorbance index (E1cm1%) of 272-292. U.S. Pat. No. 4,104,470 describes a method for the preparation of monohydrated cefazolin sodium. U.S. Pat. No. 4,146,971 describes a method for the preparation of a rapidly dissolving cefazolin sodium crystal. U.S. Pat. No. 4,898,937 describes that cefazolin sodium is placed in moisture environment to obtain α-crystals of cefazolin sodium. Above methods are not suitable for bulk production, and the resulting products are easily dehydrated to convert into other crystal forms.
CN1513854A discloses a method for preparing chelated cefazolin sodium. The examples 1-5 and 6-8 of the invention describe a method to prepare chelated cefazolin sodium from cefazolin acid by, after salt formation, adjusting pH in isopropanol solvent or a mixed solvent. The solvent means isopropanol or isopropanol+acetone, isopropanol+dichloromethane, isopropanol+ethyl acetate. In these examples, the preparation of chelated cefazolin sodium comprises following steps: 1) salt formation of cefazolin acid; 2) pH regulation; 3) addition of solvent. This invention has following problems: 1) long reaction time; 2) small particle size of the product, it has been proved in practice that the average particle size of the product obtained in the examples of this invention is about 15 microns; 3) the chelated cefazolin sodium crystal obtained in the examples of this invention is a monoclinic crystal, with a space group of P21.